NR 565 MIDTERM QUESTIONS AND ANSWERS

NR 565 MIDTERM QUESTIONS AND
ANSWERS


AG-
Protienpocoupledporeceptorspoandpohowpotheypointeractpowithpodrugspo-
poans--G-

proteinpocoupledporeceptorspo(GPCR)pointeractpowithpodrugspothrough
po7poregionspoofpoproteinspothatpospanpoandpoinnervatepothepocellpomem

branepoandpotrappothepomoleculepointopotheporeceptorpositepolikepoanpoin
terwovenpobasketpo(Inselpo&poSriram,po2018).poDrugspocanpothenpoent
erpothispospacepoandpointeractpowithpothepoGRCP.poApospecificpointeract
ionpoandpobindingpowithpoapositepoonpoonepoorpomorepoofpotheporegionspo
ofpoproteinspowithinpothepoGPCR,poandpodrugspoboundpowithpothepoGR
CPpocanpostimulatepotheporeleasepoofpoGpoproteinspothatpocanpointeractp
owithpovariouspoeffectorpoproteinspotopocreatepophysiologicalporespons

espowithinpothepobodypo(Inselpo&poSriram,po2018).poThispoprocesspoocc
urspothroughposecondarypomessengerspo(suchpoaspocAMP)powhichpocr
eatespothepoextracellularpointeractionspoproducedpobypothepodrugpobin
dingpotopothepoGRCP.

Whatponeurotransmitterspoarepoexcitatory?po-poans--
aminopoacidsposuchpoaspoglycine,poaspartate,poandpoglutamatepoarepoe
xcitatorypo(Woopo&poRobinson,pop.16,po2016).

WhichpoispothepomostpocommonpoCYPpoenzymepoinpothepobody?
poWhatporolepodoespoitpoplay?po-poans--

Accordingpotopothepotextbook,pothepoCYP3A4poispothepomostpoimportan

,tpoenzymepoinpothepobody.poCYP3A4poisporesponsiblepoforpothepometab
olismpoofpomorepothanpo50%poofpomedicationspoandpoispoconsideredpoap
omajorpodrugpometabolizingpoenzyme.poCYP3A4pocanpobepofoundpoinpo

thepoliver,poaspowellpoaspothepoliningpoofpothepoGIpotract.poDuepotopothispol
ocation,pofoodpocanpoalsopoinfluencepothispoCYP.poOnepoexamplepoofpot
hispoispograpefruitpojuice,powhichpocanpoinhibitpoCYP3A4.poMedications
pothatpoarepometabolizedpobypoCYP3A4poincludepoantimicrobials,pocalc

iumpochannelpoblockers,poantihistamines,poanticonvulsants,poazolepoa
ntifungals,poandpocorticosteroidspo(Woo,po&poRobinson,po2016).

Whatpoispothepoclinicalposignificancepoofpobeingpoanpoultra-
rapidpoCYP2D6pometabolizer?po-poans--Peoplepowhopoarepoultra-
rapidpometabolizerspohavepohighpoactivitypoofpoCYP2D6poenzymespoth
atpobreakpodownpocertainpomedicinesporapidlypoandpoarepolikelypotopone
edpodifferentpodosespoorpoevenpoapodifferentpomedicine.poDrugpodose,po
response,poandpotoxicityporiskpoofpobeta-
blockers,poantidepressants,poantiarrhythmics,poandpoopioidpoanalgesi
cspoarepodependentpoonpoCYP2D6popharmacogeneticspo(Ayazsevenp
oetpoal.,po2020).poKnowingpotheporesultpoofpothepoCYP2D6potestpoandpow

hichpogrouppothepopatientpofallspointoposuchpoaspopoorpometabolizers,poi
ntermediatepometabolizers,poorpoultra-
rapidpometabolizers,powillpohelpponursepopractitionerspoprescribepothep
orightpomedicationpoandpodosagepoforpothepopatient.



WhatpowouldpobepothepoconcernpoifpoapodrugpoispoapoCYP450indicer?
poHowpothatpomightpoaffectpothepometabolismpoofpoanotherpodrugpothepo

patientpoispotaking?po-poans--
CytochromepoP450poenzymespoarepoinpocellspothroughoutpothepobody,
poprimarilypofoundpoinpoliverpocellspo(Girvanpo&poMunro,po2016).poThese

poenzymespoarepoessentialpoforpothepometabolismpoofpomanypomedicati

ons.poCytochromepoP450poenzymespocanpoactpoaspoanpoinducerpoorpoi
nhibitorpoofpometabolism.poWhenpoapomedicationpoinducespothepoCYP
450poenzymepothatpoincreasespotheporatepoofpometabolismpo(Girvanpo&
poMunro,po2016).poThispocanpoimpactpothepoeffectivenesspoofpootherpom

edications.poForpoexample,pomedicationpoApoinducespoCYP450poenzy

, mepoactivity,pothereforepomedicationpoBpowillpobepometabolizedpoquick
erpoandpohavepoapolesspotherapeuticpoeffect.

ExplainpotheposignificancepoofpoapodrugpobeingpoanpoinhibitorpoofpoP-
glycoprotein?po(seepotext)po-poans--P-glycoproteinpo(P-
gp)poispothepomainpobarrierpoofpothepobodypoandpoitpoaffectspothepoproper
podeliverypoofpodrugspoandpocausespodrugporesistancepoinpoourpobody.po

P-
gppoispoanpoeffluxpomembranepotransporter,pothatpocanpobepofoundpothr
oughoutpothepobodypoandpoitpocontrolspothepocellularpouptakepoandpothe
podistributionpoofposyntheticposubstances,pochemicals,poandpotoxins.po

DrugspoarepochemicalspoandpoP-
gppohinderspothepoabsorption,popermeability,poandporetentionpoofpothepo
drugs,poextrudingpothempooutpoofpothepocells.poThispoadverselypoaffects
podrugpotherapiespoandpofailspotopoyieldpogoodporesults,poforpoexamplepoi

npotherapiespolikepousingpochemopoagentspoinpocancerpotreatments.poIn
pothispocase,poproperpoinhibitionpoofpoP-

gppoispoimportantpotopoincreasepocellularpouptake,potransport,poandpoha
lf-livespoofpodrugs.poThepodrugpoispoanpoinhibitorpoofpoP-
gppothatpowouldpohelppoinpothepocost-
effectivepotreatmentpoforpodiseasepoconditionspowithoutpowastingpoanpo
extrapoamountpoofpomedicines.poItpowillpohelppotoposhortenpothepotreatm
entpotimepoandpospeedyporecoverypoofpothepopatientpo(Abebepoetpoal.,po
2019;poWoopo&poRobinson,po2016).

SignificancepoofpoapoVCORC1pomutationpoforpopatientspotakingpowarfa
rin?po-poans--
Inpo2008,pothepoU.SpoFoodpoandpoDrugpoAdministrationpoupdatedpothep
odosingpoofpowarfarinpotopoincludepothepoapplicationpoofpopharmacogen

omics.poVariablepometabolismpobypoCYP2C9powaspooncepoknownpoasp
othepomajorpocontributorpotopothepovariableporesponsepotopowarfarin.poH

owever,poapomutationpoinpoVCORC1pohaspobeenpofoundpotopoaccountpo
forpomuchpomorepovariabilitypoinpowarfarinporesponsespoandpocanpocau
sepoaporareposyndromepoofpowarfarinporesistance.poApomutationpoinpoVC
ORC1poencodespoaposubunitpoofpothepovitaminpoKpoepoxideporeductas